The major objective of this proposal is to examine non-invasive methods of assessing periodontal disease activity in specific periodontal lesions in an animal model of periodontal disease. The cynomolgus monkey (Macaca fascicularis) will be used because this animal will predictably develop actively-destructive periodontal lesions following the placement of a ligature around a tooth. Previous studies have documented that both the histology and microbiology associated with these lesions are similar to human periodontal disease. Alterations in complement and specific antibodies in gingival fluid from individual experimental and control sites in the cynomolgus monkey will be measured during naturally-occurring gingivitis, health, experimental gingivitis, the initiation and progression of ligature-induced periodontitis, and following periodontal therapy. Complement will be evaluated by a multilayer crossed-immunoelectrophoresis technique which permits simultaneous assessment in gingival fluid from a specific periodontal site of complement components C3 and its cleavage product C3c of the terminal pathways, C4 and its cleavage product C4c of the classical pathway, and B and its cleavage product Bb of the alternative activating pathway. The titer of gingival fluid and serum antibodies specifically reactive with three target microorganisms (Bacteroides gingivalis, Capnocytophaga sputigena, and Fusobacterium nucleatum) associated with the induction of periodontitis in the cynomolgus monkey will be assessed throughout the experimental period by an enzyme-linked immunosorben assay. Specific subgingival bacteria will be monitored to allow interpretation of the measurements of local complement cleavage and local antibody titers. Clinical disease status will be defined by a variety of clinical measurements and subtraction radiography. The application of these sensitive immunologic methods to document subtle changes in local host response prior to and/or during tissue destruction in the monkey model may prove useful in predicting or indicating disease activity at a specific site and may provide insight into the mechanisms of periodontal tissue destruction. Such knowledge may lead to a better understanding of the disease process and may be useful in developing strategies for treatment of actively-destructive periodontal disease at individual sites.